We propose to test the hypothesis that ischemic myocardial tissues release neutrophil chemotactic factors (NCF) which stimulate the recruitment of neutrophils from the circulation into ischemic and infarcted areas of the heart. Our preliminary studies support this hypothesis since high levels of NCF were recovered in dog serum following 1 hr. occlusion of the left circumflex coronary artery then reperfusion for 1 and 2 hrs. The appearance of NCF in the serum correlated with neutrophil accumulation into ischemic areas of the heart following 2 hrs. reperfusion. Studies proposed here will: (1)Characterize the release of NCF from two models of ischemic dog hearts, including: a) occlusion of the LCx coronary artery for 1 hr. followed by reperfusion for 1, 3, and 6 hrs. (Model 1). b) non occluded arrested hearts for 1 hr. followed by reperfusion for 1, 3 and 6 hrs. (Model 2). (2)Purify the cardiac-derived NCF and develop an enzyme linked immune assay (ELISA) system. (3)Determine the biological significance of the release of NCF from ischemic hearts. Using ELISA developed specifically for cardiac NCF, we will determine the levels of NCF in serum of experimentally-induced myocardial ischemia in dogs (Model 1 and Model 2), before surgery, during surgery and postoperatively for up to 7 days. The levels of NCF will be correlated with the extent of neutrophil accumulation into ischemic (i.e. 1, 3 and 6 hrs.) and infarcted (i.e., 1, 3 and 7 days) areas of the heart. Standard modified Boyden chambers will be used to assay for NCF. Neutrophils will be isolated from dog blood and used as indicator cells. These studies will examine a mechanism by which cardiac tissues participate in the pathogenesis of cardiac inflammation associated with myocardial ischemia by releasing NCF which stimulate neutrophil recruitment into ischemic areas.
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